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Stanford University School of Medicine

Tiny bubbles raise hope for biopsy-free cancer diagnosis

A Stanford Medicine team has developed a compelling way to diagnose cancer without a biopsy. In the technique, patients are intravenously injected with bubbles a little smaller than human red blood cells. The microbubbles, which are capable of latching onto the cancer cells but not healthy cells, sail through the blood vessels until they reach a malignant tumor, where they begin to accumulate in the blood vessels supplying the tumor.

Ordinary ultrasound picks up the bubbles, distinguishing between malignant tumors, which have accumulated lots of microbubbles, and benign tumors, which have few or none.

The team, led by radiologists Jürgen Willmann, MD, and Sanjiv "Sam" Gambhir, MD, PhD, successfully tested the technique in ovarian cancer and in breast cancer. A paper describing their work was published today in the Journal of Clinical Oncology.

As explained in our news release:

Medical microbubbles are spheres of phospholipids, the same material that makes up the membranes of living cells. The bubbles are 1 to 4 microns in diameter, a little smaller than a red blood cell, and filled with a harmless mixture of perfluorobutane and nitrogen gas.

Ordinary microbubbles have been approved by the Food and Drug Administration and in clinical use for several years now. But such microbubbles, a kind of ultrasound "contrast agent," have only been used to image organs like the liver by displaying the bubbles as they pass through blood vessels. Up to now, the bubbles couldn't latch onto blood vessels of cancer in patients.

The microbubbles used in this study were designed to bind to a receptor called KDR found on the tumor blood vessels of cancer but not in healthy tissue. Noncancerous cells don't have such a receptor. Under ultrasound imaging, the labeled microbubbles, called MBKDR, show up clearly when they cluster in a tumor. And since benign breast and ovarian tumors usually lack KDR, the labeled microbubbles mostly passed them by.

This study was a small, preliminary safety trial, and the researchers are now moving forward with a larger phase-2 one.

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